Bupivacaine is available as a racemic mixture of its enantiomers, d-bupivacaine and l-bupivacaine (LB). The aim of this randomized, double-blind study was to investigate the clinical efficacy and safety of S(-)-bupivacaine compared with standard racemic bupivacaine (RB) in horses under caudal epidural analgesia. Two treatments were administered to each horse, with a 2-week interval between subsequent treatments. Treatment 1 consisted of 0.5% LB at a dose of 0.06 mg/kg of body weight, and treatment 2 consisted of 0.5% RB at a dose of 0.06 mg/kg of body weight. Epidural injections were given in all animals between the first and second coccygeal vertebra. Heart rate (HR), arterial pressures, respiratory rate (RR), rectal temperature (RT), analgesia, and motor blocking were determined before drug administration (basal) and 5, 10, 15 and 30 min after drug administration, and at 30 min intervals thereafter. There were no significant differences between the two treatments in the quality of sensory and motor block. The duration of analgesia was 320 +/- 30 min (mean +/- SD) for RB and 360 +/- 42 min for LB. HRs and RRs, arterial pressures and RT did not change (P < 0.05) significantly from basal values after epidural administration of LB or RB. This study supports that 0.5% LB is an effective alternative to RB in caudal epidural analgesia in conscious, standing horses. The use of LB vs. RB warrants further investigation, particularly for long-lasting surgery in the perineal region.